Protein kinase C-alpha is an upstream activator of the IkappaB kinase complex in the TPA signal transduction pathway to NF-kappaB in U2OS cells
| Autor: | Gilles Courtois, van der Eb Aj, A. Zantema, Shoji Yamaoka, Kuiperij Hb, Alfred C.O. Vertegaal |
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| Rok vydání: | 2001 |
| Předmět: |
MAPK/ERK pathway
Indoles Protein Kinase C-alpha MAP Kinase Kinase 1 IκB kinase Protein Serine-Threonine Kinases Maleimides chemistry.chemical_compound NF-KappaB Inhibitor alpha Multienzyme Complexes Nitriles Butadienes Tumor Cells Cultured Humans CHUK Protein kinase C Protein Kinase C Genes Dominant Mitogen-Activated Protein Kinase Kinases Activator (genetics) Tumor Necrosis Factor-alpha Ribosomal Protein S6 Kinases NF-kappa B NF-κB Cell Biology Molecular biology I-kappa B Kinase DNA-Binding Proteins Enzyme Activation Isoenzymes IκBα Kinetics chemistry Mutation Tetradecanoylphorbol Acetate I-kappa B Proteins Signal transduction Mitogen-Activated Protein Kinases Protein Processing Post-Translational Signal Transduction |
| Zdroj: | Cellular signalling. 12(11-12) |
| ISSN: | 0898-6568 |
| Popis: | Inactive nuclear factor kappaB (NF-kappaB) complexes are retained in the cytoplasm by binding to inhibitory proteins, such as IkappaBalpha. Various stimuli lead to phosphorylation and subsequent processing of IkappaBalpha in the 26S proteasome and import of the active NF-kappaB transcription factor into the nucleus. In agreement with our previous finding that p90(rsk1) is essential for TPA-induced activation of NF-kappaB in Adenovirus 5E1-transformed Baby Rat Kidney cells, we now report that the MEK/ERK/p90(rsk1) inhibitor U0126 efficiently blocks TPA-induced IkappaBalpha processing in these cells. However, in U2OS cells, the cytokine-inducible IkappaB kinase complex (IKK) is the essential component of the TPA signal transduction pathway. Activation of the IKK complex in response to TPA is mediated by PKC-alpha, since both the PKC inhibitor GF109203 and a catalytically inactive PKC-alpha mutant inhibit activation of endogenous IKK by TPA, but not by tumor necrosis factor-alpha (TNF-alpha). We conclude that IKK is an integrator of TNF-alpha and TPA signal transduction pathways in U2OS cells. |
| Databáze: | OpenAIRE |
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